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Block 4: Pharmacotherapy of Thyroid Diseases PHS 933
Terms in this set (92)
What are the main functions of TH
development and metabolic homeostasis
A lack of thyroid hormone in infants causes what condition?
cretinism (dwarfism, mental retardation, listlessness)
What are three common symptoms of a lack of thyroid hormone in adults?
weight gain, fatigue, cold intolerance
The thyroid makes two _______-containing hormones.
What are the two iodine-containg hormones produced by the thyroid?
T4 (thyroxine), T3 (triiodothyronine)
What is the precursor protein that T4 and T3 are made from
What is the active form of thyroid hormone, T3 or T4?
On what protein are T4/T3 transported when in the blood?
TBG (binds T3 with less affinity)
What two other proteins bind T4
transthyretin and albumin
What is the role of the thyroid peroxidase enzyme?
activates iodine to hypoiodite (IO) for coupling to tyrosines on thyroglobulin
T4 and T3 are released from iodinated thyroglobulin by ___________ proteolysis.
What hormone initiates the release of T3 and T4 from the iodinated thyroglobulin?
thyroid stimulating hormone (TSH)
thyroid stimulating hormone
How are T3 and T4 transported in the blood?
bound to thyroxine-binding-globulin (TBG)
Which hormone, T3 or T4, binds to thyroxine-binding globulin with greater affinity?
What are 7 factors that increase thyroxine binding and decrease free T4/T3
6. liver disease
What are four factors that decrease thryoxing-binding globulin binding and increase free T3/T4 levels?
1: glucocorticoids, 2: androgens, 3: anti-epileptics, 4: furosemide
Which thyroid hormone, T3 or T4, is more stable?
Where is TSH (thyroid stimulating hormone) released from?
What hormone regulates TSH (thyroid-stimulating hormone) release?
thyrotropin-releasing hormone (TRH)
What are four effects of TSH (thyroid stimulating hormone) on the thyroid?
1: increased T4 (thyroxine) release,
2: increased iodide uptake,
3: increased thyroglobulin synthesis,
4: increased thyroglobulin proteolysis
Where do T4/T3 act to decrease their release?
hypothalamus and pituitary
Where is TRH (thyrotropin-releasing hormone) released from?
In a _________ goiter, the thyroid may still be functioning okay, but needs more iodine (so undergoing hypertrophy to better extract it from the blood).
What levels would you see in moderate iodine deficiency?
decreased T4/T3 and increased TSH
The most common thyroid disorder is _____(hypo/hyper)-thyroidism.
________ hypothyroidism is due to failure of thyroid to make T4 (thyroxine), while __________ hypothyroidism results from loss of pituitary function and TSH.
primary and secondary
Does measurement of total thyroid hormone concentration provide an accurate reflection of thyroid function?
not necessarily (outcome affected by amount or affinity of TBG)
Measuring levels of what hormone is most commonly used for a thyroid function test?
TSH (thyroid stimulating hormone, is an indicator of free T4 levels)
In primary hypothyroidism, TSH levels should be __________, while in secondary hypothyroidism TSH levels should be __________.
increased and decreased
What substance is used to test the ability of the thyroid to respond to TSH
What food sources are rich in iodine
fish, dairy, salt
Severe iodine deficiency leads to what
hypothyroidism and cretinism
What is the drug of choice to treat hypothyroidism?
How should levothyroxine be administered
in the morning on an empty stomach 30-60min before breakfast
-doses should be titrated every 6 weeks based on TSH levels
Chronic autoimmune thyroiditis is also known as __________ Disease (most common cause of hypothyroidism when iodine sufficient).
Hashimoto's (antibodies to thyroid peroxidase or thyroglobulin)
What is congenital hypothyroidism/cretinism caused by
severe iodine deficiency
What special populates warrant special considerations for levothyroxine
elderly (lower dose)
pregnant women (higher) do to increase TBG
How are pregnancy and hypothyroidism related
pregnancy can reveal latent hypothyroidism
-must be treated in the first trimester to prevent miscarriage
What risks are associated with not treating hypothyroidism in pregnancy
What are physical characteristics of patients with hypothyroidism
expressionless puffy face
cold dry skin
brittle hair and fingernails
SQ thickening and edema
husky low pitched voice
impaired cognition and depression
weight gain, lethargy, fatigue
What are common characteristics of cretinism recognized at 3-5m
puffy expressionless face
dry, yellow skin
What three risk factors increase the risk of developing hypothyroidism
other autoimmune disorders
family Hx of autoimmune disorders
Why is it not necessarily a huge deal if you miss a dose of levothyroxine?
b/c it has a half-life of 7 days (so will still have drug present even if miss a dose, takes at least 6 wks to reach a new steady-state after dose changes)
What is myxedema?
severe hypothyroidism (thickening and swelling of the skin)
What are characteristics of myxedema
thickening and swelling of skin
respiratory depression, hypothermia, bradycardia
amplified symptoms of hypothyroidism
Who is susceptible and when
elderly during the winter, especially women
-triggered by infection of CVD
How is myxedema treated
-myxedema coma requires emergency treatment
-synthetic T3- liothyronine
-T4 given IV
What is the most common endocrinopathy?
nodular thyroid disease (50% of people by 50)
What are the risks of nodular thyroid disease
How is nodular thyroid disease treated
-observing thyroid and allowing the lumps to shrink on their own
-radioactive iodine if noncancerous
Are TSH levels usually low or high in hyperthyroidism?
low (except in pituitary adenomas)
How is thyrotoxicosis diagnosed?
increased iodine uptake into thyroid (elevated levels of T3 and T4)
Hyperthyroidism is also known as _________ disease.
What is the most common cause of hyperthyroidism?
autoimmune disorder (IgG antibodies bind to/activate the TSH receptor)
What is a common characteristic of hyperthyroidism?
exophthalmos (bulging eyes) due to inflammation of periorbital tissues
What are four signs/symptoms of hyperthyroidism?
excessive heat generation
muscle wasting and osteoporosis
rapid forceful heart beat
The presence of _________ compounds in cruciferous vegetables (cabbage, Brussels sprouts, broccoli) inhibits thyroid peroxidase, which prevents the incorporation of iodine into tyrosines of thyroglobulin (inhibits creation of thyroid hormones).
(lead to creation of thioureylene drugs)
What are the two thioureylene drugs
propylthiouracil and methimazole
How does propylthiouracil (PTU) additionally help treat hyperthyroidism?
inhibits peripheral conversion of T4 (thyroxine) to T3 (triiodothyronine, active form)
makes it first line for severe disease
How long is the typical treatment for hyperthyroidism disease?
4-8 wks with large dose and then maintenance dose for 1-2 years
What is the relapse rate of anti-thyroid meds
30-50% when DC maintenance dose
-older pts, prompt Tx, and small goiters, controlled decrease in dosage are least likely to relapse
How are hyperthyroid relapses treated
radioactive iodine, thyroid surgery, administer drug
What are alternative treatments for hyperthyroidism
thyroidectomy and anti-thyroid drugs
Effective hyperthyroidism treatment will result in what?
reduction of size of goiter
How are thioureylenes dosed?
high dose in the beginning and then tapered to a maintenance dose
What can result from overtreatment of hyperthyroidism
return of goiter and hypothyroidism
What is the most serious adverse effect of propylthiouracil or methimazole therapy for Grave's disease treatment?
What signs should patients report while taking a thioureylene
(means they have agranulocytosis)
Do PTU and MMI have cross sensitivity?
no but urticarial rash is common
How can corticosteroids like dexamethasone be effective as an adjuvant therapy in Grave's disease?
suppresses conversion of T4 to T3 (also suppresses immunoreactivity)
What is the MOA of thiocyanate for hyperthyroidism treatment?
is an ionic inhibitor (interferes with thyroid's ability to take up iodide)
What two substances can thiocyanate be found
cabbage and cigarette smoke (smoking worsens hypothyroidism)
How can lithium cause hypothyroidism?
decreases T4 (thyroxine) and T3 (triiodothyronine) secretion
Why is perchlorate contamination in water a concern?
causes fatal aplastic anemia (10x more potent than thiocyanate)
High concentrations of iodine ________ all aspects of iodine metabolism by the thyroid (can be used in hyperthyroidism).
suppress (decreases I- uptake into cells, inhibits synthesis of iodotyrosines and iodothyronine, inhibits release of thyroxine)
How does I- treat hyperthyroidism
resolves nontoxic goiter
How quickly does Iodine work to decrease hyperthyroidism
metabolic rate falls within 24 hours
max effect in 10-15d
What is the most common iodine isotope and what particles does it emit
gamma and beta
What iodine isotope is used for thyroid scans and what particles does it emit?
How is radioactive iodine used to treat hyperthyroidism
131 given orally as NaI to destroy the thyroid and then treat for hypothyroidism
What are three advantages to using radioactive iodine
no loss of parathyroid glands
no risk of death/cancer
What is the disadvantage to using radioactive iodine
Who is most appropriate for treatment with radioactive iodine
older patients with heart disease and toxic goiter (does not go into remission)
What is thyroid escape?
when treated with iodine, hyperthyroidism returns over time, more severe
-this is why iodine is only used before a thyroidectomy
Amiodarone (an antiarrhythmic med) is a medical source of __________.
What is the "thyroid storm?"
life-threatening exacerbation of hyperthyroidism (usually precipitated by a secondary illness in thyrotoxic)
What are five symptoms of the "thyroid storm?"
fever (greater than 101 F),
What are three ways to treat symptoms of the "thyroid storm?"
2. Iodine administered 1 hr after thionamide to block release of preformed thyroid hormone
3. beta blockers/Ca channel blockers
5. IV fluids, antipyretics, sedatives
Why is iodide used for protection against radioactive fallout?
it saturates the thyroid with nonradioactive iodine to prevent the thyroid from absorbing iodine to prevent thyroid cancer and hypothyroidism, cretinism
What are medical sources of iodine
radio contrast agents
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